© The Rockefeller University Press,
0021-9525/1998//1073 $5.00
The Journal of Cell Biology, Volume 141, Number 4,
, 1998 1073-1081
Modulation of Integrin Activity is Vital for Morphogenesis
Maria D. Martin-Bermudo,
Olga M. Dunin-Borkowski, and
Nicholas H. Brown
Wellcome/CRC Institute, Cambridge CB2 1QR, England; and Department of Biochemistry, Cambridge University, Cambridge CB2 1QW, England
Cells can vary their adhesive properties by modulating the affinity of integrin receptors. The activation and inactivation of integrins by inside-out mechanisms acting on the cytoplasmic domains of the integrin subunits has been demonstrated in platelets, lymphocytes, and keratinocytes. We show that in the embryo, normal morphogenesis requires the
subunit cytoplasmic domain to control integrin adhesion at the right times and places. PS2 integrin (
PS2βPS) adhesion is normally restricted to the muscle termini, where it is required for attaching the muscles to the ends of other muscles and to specialized epidermal cells. Replacing the wild-type
PS2 with mutant forms containing cytoplasmic domain deletions results in the rescue of the majority of defects associated with the absence of the
PS2 subunit, however, the mutant PS2 integrins are excessively active. Muscles containing these mutant integrins make extra muscle attachments at aberrant positions on the muscle surface, disrupting the muscle pattern and causing embryonic lethality. A gain- of-function phenotype is not observed in the visceral mesoderm, showing that regulation of integrin activity is tissue-specific. These results suggest that the
PS2 subunit cytoplasmic domain is required for inside-out regulation of integrin affinity, as has been seen with the integrin
IIbβ3.
Address all correspondence to Nicholas Brown, Wellcome/CRC Institute, Tennis Court Road, Cambridge CB2 1QR, England. Tel.: 44-1223-334-128; Fax: 44-1223-334-089; E-mail: nb117{at}mole.bio.cam.ac.uk
1. Abbreviation used in this manuscript: PS, position-specific.

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